Very promising recent observational data reveal that exclusive breastfeeding can substantially reduce the rate of postnatal maternal to child transmission (MTCT) of HIV6-9. The incidence of MTCTA is H 25% among untreated HIV-infected women in Sub-Saharan Africa, accounting for > 2-300,000 children infected/year. Protection achieved with prenatal antiretroviral therapy (ART) may be lost in the post-natal period with persistent exposure to the virus in milk. Indeed, breastfeeding causes 25-44% of MTCT. Rates of HIV transmission are extremely high (0.7-1% per week) in the early postnatal period from birth to 4-6 weeks. Recent clinical trials to prevent MTCT are somewhat disappointing. However, for late postnatal transmission (6 weeks to e 6 months), practicing exclusive rather than mixed breastfeeding in the first 3 months is associated with > 2 fold reduction in infant HIV infection. In exclusive breastfeeding (EBF), breast milk alone is given with no additional fluids or foods, whereas with mixed feeding (MBF), other foods are introduced early. The probability of practicing EBF has increased with specific and substantial counseling interventions. We propose to identify the biological consequences of feeding practices (EBF vs. MBF) that may plausibly contribute to the risk of postnatal HIV infection. We propose to characterize the impact of breastfeeding practices on the microbiologic, immunologic, and inflammatory status of both the mother's milk and infant intestine as determinants of risk for transmission of HIV to infants. PUBLIC HEALTH RELEVANCE: Breast milk transmission accounts for a third to a half of the 1500 cases of maternal-to-child-transmission of HIV every day (1 per minute). Interventions to limit these infections have been few. New data suggest that exclusive breastfeeding (no other foods), compared with mixed feeding, may significantly decrease these rates while retaining the protective effects of breast milk against pneumonia, diarrhea, and death. We propose to characterize the mechanisms of this protection to define effect strategies to protect these children.